Bruderer, Roland M.; Brasseur, Catherine; Meyer, Hemmo:
The AAA ATPase p97/VCP interacts with its alternative co-factors, Ufd1-Npl4 and p47, through a common bipartite binding mechanism
In: The Journal of Biological Chemistry (JBC), Vol. 279 (2004), No. 48, pp. 49609 - 49616
2004article/chapter in journal
Biology
Related: 1 publication(s)
Title:
The AAA ATPase p97/VCP interacts with its alternative co-factors, Ufd1-Npl4 and p47, through a common bipartite binding mechanism
Author:
Bruderer, Roland M.;Brasseur, Catherine;Meyer, HemmoUDE
GND
1089446616
LSF ID
51479
ORCID
0000-0003-1883-1796ORCID iD
Other
connected with university
Year of publication:
2004

Abstract:

The AAA ATPase p97/VCP forms complexes with different adapters to fulfill distinct cellular functions. We analyzed the structural organization of the Ufd1-Npl4 adapter complex and its interaction with p97 and compared it with another adapter, p47. We found that the binary Ufd1-Npl4 complex forms a heterodimer that cooperatively interacts with p97 via a bipartite binding mechanism. Binding site 1 (BS1) is a short hydrophobic stretch in the C-terminal domain of Ufd1. The second binding site is located at the N terminus of Npl4 and is activated upon binding of Ufd1 to Npl4. It consists of about 80 amino acids that are predicted to form a ubiquitin fold domain (UBD). Despite the lack of overall homology between Ufd1-Npl4 and p47, both adapters use identical binding mechanisms. Like the ubiquitin fold ubiquitin regulatory X (UBX) domain in p47, the Npl4-UBD interacts with p97 via the loop between its strands 3 and 4 and a conserved arginine in strand 1. Furthermore, we identified a region in p47 homologous to Ufd1-BS1. The UBD/UBX and the BS1 of both adapters interact with p97 independently, whereas homologous binding sites in both adapters compete for binding to p97. In contrast to p47, however, Ufd1-Npl4 does not regulate the ATPase activity of p97; nor does a variant of p47 that contains both binding sites but lacks the N-terminal domains. Therefore, the binding sites alone do not regulate p97 directly but rather serve as anchor points to position adapter-specific domains at critical locations to modulate p97-mediated reactions.